CIML-NK Cells for Acute Myeloid Leukemia

Overseen By Caitlin Cottrell

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Children's Hospital Medical Center, Cincinnati

Must not be taking: Prednisone, Investigational therapies

Disqualifiers: CNS disease, APML, Uncontrolled infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new treatment using enhanced donor immune cells for patients with tough-to-treat leukemia. These special cells are designed to better remember and attack cancer cells. The goal is to see if this approach is safe and effective for these patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude participants who are taking more than 10mg of prednisone (a type of steroid) daily or more than 0.5mg/kg of prednisone daily. It also excludes those on other investigational treatments.

What data supports the effectiveness of the treatment Cytokine-Induced Memory-Like Natural Killer Cells (CIML-NK) for Acute Myeloid Leukemia?

Research shows that CIML-NK cells, which are enhanced natural killer cells, have been effective in treating acute myeloid leukemia (AML). In clinical trials, these cells have led to complete remissions in some patients with AML, and they have shown enhanced ability to fight leukemia cells both in lab studies and in patients. ^{1 2 3 4 5}

Is the CIML-NK cell treatment safe for humans?

Using CIML-NK cells in cancer treatment, including for acute myeloid leukemia, has been found to be safe in clinical trials, with some patients experiencing complete clinical remissions. ^{2 4 5 6 7}

How is the CIML-NK cell treatment different from other treatments for acute myeloid leukemia?

CIML-NK cells are unique because they are natural killer cells that have been 'trained' with specific cytokines (proteins that help cells communicate) to remember and attack leukemia cells more effectively. This memory-like feature allows them to persist longer and respond more robustly compared to standard NK cells, making them a promising option for treating acute myeloid leukemia. ^{1 2 4 7 8}

Research Team

Zahra Hudda

Principal Investigator

Children's Hospital Medical Center, Cincinnati

Eligibility Criteria

Adults diagnosed with relapsed or refractory acute myeloid leukemia (AML) who have a compatible family donor can join this trial. They must have at least 5% AML cells in their bone marrow and be able to perform daily activities at least half of the time. People with certain heart, lung, liver issues, uncontrolled infections, or on high-dose steroids cannot participate.

Inclusion Criteria

My leukemia did not respond well to initial treatments.

I am 12 years old or older.

I have a closely related donor who is a partial genetic match for me.

Exclusion Criteria

My heart's pumping ability is below 45%.

Pulmonary Function: Oxygen saturation <92% on room air

Known allergy or hypersensitivity reaction to IL-2 injections

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepleting Chemotherapy

Participants receive a lymphodepleting chemotherapy regimen to prepare for CIML-NK cell infusion

1-2 weeks

CIML-NK Cell Infusion

Cytokine-induced memory-like NK cells are infused into participants

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after CIML-NK cell infusion

4 weeks

4 visits (in-person)

Long-term Follow-up

Participants are assessed for clinical response and ability to proceed to hematopoietic stem cell transplant

6 months

Treatment Details

Interventions

• Cytokine-Induced Memory-Like Natural Killer Cells (CIML-NK)

Trial Overview The study is testing if natural killer cells treated with cytokines from a relative's donated cells are safe and effective for treating AML that has come back or hasn't responded to other treatments.

Participant Groups

Group I: Cytokine-Induced Memory-Like Natural Killer (CIML-NK) Cells Experimental Treatment 1 Intervention

The investigational cell product is a cytokine-induced memory-like natural killer cell preparation, derived from the recipient's haploidentical donor's apheresis product.

Cytokine-Induced Memory-Like Natural Killer Cells (CIML-NK) is already approved in United States for the following indications:

Approved in United States as CIML-NK cells for:

• Relapsed or refractory acute myeloid leukemia (AML)

Who Is Running the Clinical Trial?

Children's Hospital Medical Center, Cincinnati

Lead Sponsor

Trials

844

Recruited

6,566,000+

Findings from Research

Cytokine-induced memory-like NK cells show enhanced ability to produce interferon-γ and kill leukemia cells, making them a promising option for treating acute myeloid leukemia (AML).

In a first-in-human phase 1 clinical trial, memory-like NK cells were successfully expanded in AML patients, leading to clinical responses in five out of nine patients, including four complete remissions, indicating their potential effectiveness as an immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytokine-induced memory-like natural killer cells exhibit enhanced responses against myeloid leukemia. Romee, R., Rosario, M., Berrien-Elliott, MM., et al.[2021]

Cytokine-induced memory-like (CIML) NK cells, which are generated through brief stimulation with IL-12, IL-15, and IL-18, show enhanced effector functions and long-term persistence, making them promising candidates for cancer immunotherapy.

Clinical trials have demonstrated that infusions of CIML NK cells are safe and have led to complete clinical remissions in patients with relapse/refractory acute myeloid leukemia (AML).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytokine-Induced Memory-Like NK Cells: From the Basics to Clinical Applications. Terrén, I., Orrantia, A., Astarloa-Pando, G., et al.[2022]

In a clinical trial involving 15 patients with relapsed/refractory acute myeloid leukemia (AML), the use of donor-derived memory-like (ML) NK cells combined with N-803 (an IL-15 superagonist) was well tolerated and resulted in an impressive 87% of patients achieving a composite complete response within 28 days.

The ML NK cells showed significant expansion and persistence, remaining the dominant lymphocyte population for over 2 months post-transplant, and exhibited enhanced antitumor functions compared to conventional NK cells, indicating their potential as an effective immunotherapy strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hematopoietic cell transplantation donor-derived memory-like NK cells functionally persist after transfer into patients with leukemia. Berrien-Elliott, MM., Foltz, JA., Russler-Germain, DA., et al.[2023]

In a study involving 24 patients with acute myeloid leukemia (AML) and chronic myeloid leukemia (CML), the infusion of autologous cytokine-induced killer (CIK) cells did not show a survival benefit for AML patients post-transplant, nor did it significantly reduce detectable disease in CML patients.

The treatment was found to be safe, with only mild adverse reactions like fever reported, but the results suggest that further modifications to enhance the effectiveness of CIK cells are necessary for better clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I/II clinical trial of autologous cytokine-induced killer cells as adjuvant immunotherapy for acute and chronic myeloid leukemia in clinical remission. Linn, YC., Yong, HX., Niam, M., et al.[2022]

Natural killer (NK) cell-based immunotherapy shows promise in treating acute myeloid leukemia (AML) by targeting cancer cells and enhancing the immune response, particularly through the use of cytokine-induced memory-like (CIML) NK cells.

CIML-NK cells, which are pre-activated with specific cytokines, demonstrate a longer lifespan and adaptive immunity characteristics, making them a potentially effective and safe treatment option for AML, addressing the limitations of traditional NK cell therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytokine-Induced Memory-Like NK Cells: Emerging strategy for AML immunotherapy. Bakhtiyaridovvombaygi, M., Yazdanparast, S., Mikanik, F., et al.[2023]

Cytokine-induced killer (CIK) cells, derived from patients or healthy donors, show strong potential in targeting leukemia cells without harming normal hematopoietic stem cells, making them a promising option for leukemia treatment.

CIK cells can generate a graft versus tumor response while minimizing graft versus host disease, suggesting they could effectively prevent leukemia relapse after hematopoietic stem cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytokine-induced killer cells: A novel immunotherapy strategy for leukemia. Yang, XY., Zeng, H., Chen, FP.[2020]

Cytokine-induced killer (CIK) cells can be successfully expanded from patients with acute leukemia, showing a median of 35.3% CD3(+)CD56(+) cells that are effective in killing certain leukemia cells, particularly acute myeloid leukemia (AML) targets.

The study indicates that CIK cells have potential for immunotherapy in AML, as they can effectively target both autologous and allogeneic leukemia cells, suggesting their use in various treatment scenarios, including post-transplant relapses and chemotherapy-resistant cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Generation of cytokine-induced killer cells from leukaemic samples with in vitro cytotoxicity against autologous and allogeneic leukaemic blasts. Linn, YC., Lau, LC., Hui, KM.[2022]

Cytokine-induced killer (CIK) cells, derived from patients with acute myeloid leukemia (AML), show strong cytotoxicity against both autologous and allogeneic leukemia cells, making them a promising option for targeted leukemia therapy.

CIK cells do not induce graft-versus-host disease in mouse models, suggesting they can be safely used in transplants, and their infusion has been shown to prolong survival in leukemia-bearing mice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytokine-induced killer cells: NK-like T cells with cytotolytic specificity against leukemia. Linn, YC., Hui, KM.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Cytokine-induced memory-like natural killer cells exhibit enhanced responses against myeloid leukemia. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Cytokine-Induced Memory-Like NK Cells: From the Basics to Clinical Applications. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Hematopoietic cell transplantation donor-derived memory-like NK cells functionally persist after transfer into patients with leukemia. [2023]

4. England pubmed.ncbi.nlm.nih.gov

A phase I/II clinical trial of autologous cytokine-induced killer cells as adjuvant immunotherapy for acute and chronic myeloid leukemia in clinical remission. [2022]

5. France pubmed.ncbi.nlm.nih.gov

Cytokine-Induced Memory-Like NK Cells: Emerging strategy for AML immunotherapy. [2023]

6. Greece pubmed.ncbi.nlm.nih.gov

Cytokine-induced killer cells: A novel immunotherapy strategy for leukemia. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Generation of cytokine-induced killer cells from leukaemic samples with in vitro cytotoxicity against autologous and allogeneic leukaemic blasts. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Cytokine-induced killer cells: NK-like T cells with cytotolytic specificity against leukemia. [2019]